多巴胺D4受体PET显像剂^18F-FHTP的生物学评价  

Biological Evaluation of ^(18)F-FHTP as a Potential Dopamine D_4 Receptor PET Imaging Agent

作　　者：李谷才[1] 尹端沚[2] 程登峰[2] 徐万帮[2] 郑明强[2] 汪勇先[2] 

机构地区：[1]湖南工程学院化学化工系,湖南湘潭411104 [2]中国科学院上海应用物理研究所放射性药物研究中心,上海201800

出　　处：《核化学与放射化学》2008年第2期80-85,共6页Journal of Nuclear and Radiochemistry

基　　金：国家自然科学基金资助项目(30371634);湖南省自然科学基金资助项目(07JJ6014)

摘　　要：为研究多巴胺D4受体在精神分裂症、注意力缺乏多动症等疾病病因分析中的作用,开展了多巴胺D4受体PET显像剂3-(4-[18F]氟苄基)-8-羟基-1,2,3,4-四氢苯并吡喃[3,4-c]吡啶-5-酮(18F-FHTP)的体内外生物学评价。通过体外受体竞争抑制结合分析,测定了FHTP对多巴胺D2样受体的亲和性;通过辛醇实验,测定了18F-FHTP的脂水分配系数;通过大鼠体内的生物分布和阻断分布实验,测定了18F-FHTP在大鼠体内的各感兴趣区域的摄取率。实验测得FHTP对D2,D3受体的亲和常数Ki值分别大于5 800,3 000 nmol/L;对D4.2受体的Ki值为2.9 nmol/L;测得其脂水分配系数为1.11;大鼠生物分布实验显示,18F-FHTP能通过血脑屏障进入脑,并在纹状体、下丘脑、额叶皮质、海马、小脑等已知的D4受体分布区域有较高的摄取率。体外受体结合分析、脂水分布实验、大鼠体内分布和阻断分布研究表明,18F-FHTP可作为多巴胺D4受体显像剂用于体内显像研究。3-（4-fluorobenzyl）-8-hydroxy-1,2,3, 4-tetrahydrochromeno pyridin-5-one（^18F-FHTP） was in vitro and in vivo evaluated as a potential dopamine D4 receptor PET imaging agent.Through receptor binding assay,the Ki of FHTP were determined to be 2.9 nmol/L for D4.2 receptor,and to be greater than 3 000 and 5 800 nmol/L for D3 and D2 receptor,respectively.The lg P was measured to be 1.11 through octanol experiment.The regional biodistribution studies in rats were carried out through biological distribution and blocking bio-distribution experiments. The biodistributions studies show that ^18F-FHTP can penetrate through blood-brain barrier and selectively accumulate in striatum, hypothalamus, frontal cortex, hippocampus, cerebellum, where the D4 receptor is reportedly located, and among organs, lung and kidney have higher uptakes than the others. Conclusively, in vitro and in vivo biological studies demonstrate that ^18F-FHTP is a potential dopamine D4 receptor imaging agent.

关 键 词：多巴胺D4受体 PET显像剂 ^18F 生物学评价 

分 类 号：O614.62[理学—无机化学]